TW201438671A - Method for forming brain stimulation cognitive response images - Google Patents
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Abstract
Description
本發明關於一種刺激腦部認知反應圖像形成之方法,尤指一種利用碳11-2-脫氧-D-葡萄糖經由視覺、聽覺或認知刺激等外在條件,刺激腦部認知反應圖像形成之新穎方法。 The invention relates to a method for stimulating image formation of brain cognition response, in particular to using a carbon 11-2-deoxy-D-glucose to stimulate brain cognition response image formation through external conditions such as visual, auditory or cognitive stimulation. Novel approach.
大腦為人類重要的中樞神經系統,掌管人類精神、思維、體覺、聽覺、視覺等五大功能,也是人類產生心理現象的所在。人腦構造分為大腦與小腦。大腦由大腦皮質(大腦新皮質)、大腦邊緣葉(舊皮質)、腦幹、腦樑所構成。大腦皮質從位置上可分為額葉、聶葉及枕葉三部分。以往,研究者針對心智模式改變之腦部活動掃描方法只能仰賴包括如腦波儀(EEG)、腦磁波儀(MEG)、正子輻射斷層掃描(Positron Emission Tomography,PET)、單光子電腦斷層掃描(Single Photon Emission Tomography,SPECT)及功能性核磁共振造影掃描(functional Magnetic Resonance Imaging,fMRI)等技術來探討大腦的認知反應區域功能。 The brain is an important central nervous system for human beings. It is responsible for the five functions of human spirit, thinking, body sense, hearing and vision. It is also the place where human beings produce psychological phenomena. The human brain structure is divided into the brain and the cerebellum. The brain is made up of the cerebral cortex (the neocortex of the brain), the marginal leaves of the brain (the old cortex), the brain stem, and the brain. The cerebral cortex can be divided into three parts: the frontal lobe, the Nieye and the occipital lobe. In the past, researchers' brain activity scanning methods for mental model changes can only rely on, for example, electroencephalograph (EEG), brain magnetic wave (MEG), Positron Emission Tomography (PET), single photon computed tomography. (Single Photon Emission Tomography, SPECT) and functional magnetic resonance imaging (fMRI) techniques to explore the cognitive function of the brain.
以往,許多以腦造影技術而獲取大腦影像的分析方法,都預設我們所量測到隨著實驗刺激或相關事件的血液動力(hemodynamic response,HR)變化,會發生在大腦數個部位所構成的網絡上。這些分析方式反映出我們對大腦的認識仍停留在線性系統的典範下:依據大腦模組(modularity)論的架構過度簡化大腦影像「voxel」的意義,上述理論認為 「不同大腦區域負責不同認知功能」,並認為我們在大腦影像中看到的血液動力變化以及非血液動力變化(non-HR noise),在不同事件、不同腦區上仍具同質性。但隨著我們對大腦的認識越來越複雜時,就可以體認到HR的變化具有不可預測性與大腦之複雜性。 In the past, many analytical methods for acquiring brain images using brain angiography have presupposed that we have measured changes in hemodynamic response (HR) with experimental stimuli or related events, which occur in several parts of the brain. On the network. These analysis methods reflect that our understanding of the brain is still in the paradigm of linear systems: the simplification of the meaning of the brain image "voxel" based on the framework of the modular theory, the theory holds "Different brain regions are responsible for different cognitive functions," and believe that the hemodynamic changes and non-HR noise we see in brain images are still homogenous in different events and different brain regions. But as our understanding of the brain becomes more complex, we can recognize the unpredictability of HR changes and the complexity of the brain.
以功能性磁振造影和正子斷層掃描而言,雖然這兩種腦造影技術具有高空間解析度,但卻有低時間解析度的缺點,而腦波儀與腦磁波儀可量測神經組織活化時電離子流動所產生的磁場分佈與電場分佈,其具有優越之毫秒(millisecond)高時間解析度的優點,可用以探究腦網路神經元活動之時序機轉,經頭顱磁刺激之方法(Transcranial Magnetic Stimulation,TMS)則有莫大的發展空間以調理(modulate)神經網路的可塑性(plasticity)。然而,這些技術卻沒有功能性磁振造影或正子斷層掃描所擁有的高空間解析度。由於這些方法奠基於不同的醫學物理機制,所產生的影像或訊號資訊其特性也有所不同。 In terms of functional magnetic resonance imaging and positron tomography, although the two brain imaging techniques have high spatial resolution, they have the disadvantage of low time resolution, and the brain wave instrument and the brain magnetic wave instrument can measure the activation of nerve tissue. The magnetic field distribution and electric field distribution generated by the ion current flow have the advantages of superior millisecond and high time resolution, which can be used to explore the sequential rotation of brain network neuron activity, and the method of transcranial magnetic stimulation (Transcranial) Magnetic Stimulation (TMS) has a lot of room to modulate the plasticity of the neural network. However, these techniques do not have the high spatial resolution of functional magnetic resonance imaging or positron tomography. Since these methods are based on different medical physics mechanisms, the resulting image or signal information has different characteristics.
以利用放射性藥物輔助腦部造影的技術而言,目前最常使用為氟18標幟放射藥物,如[氟18]-2-去氧-D-葡萄糖(F-18 Fluoro-2-Deoxyglucose,F-18-FDG),又稱氟化去氧葡萄糖,是一個與葡萄糖的化學結構極為相似的分子,由於氟化去氧葡萄糖在生物體內的分布可依組織、器官對葡萄糖吸收代謝情形而不同,經過正子造影後,呈現出葡萄糖分子在人體的生理活動圖像,更透過定量的標準吸收值(standard uptake value,SUV)來達成診斷的功能。由於正在增生的癌細胞因快速分裂,藉著基因蛋白質調控,異常提高細胞的新陳代謝率,所以氟化去氧葡萄糖的正子造影影像上即可顯出高於正常細胞背景吸收差異。正子造影所攝得的影 像可顯現出器官或組織的分子現象。 In terms of the technique of using radiopharmaceuticals to assist brain angiography, the most commonly used radioactive drug for fluorine 18, such as [Fluoro 18]-2-deoxy-D-glucose (F-18 Fluoro-2-Deoxyglucose, F -18-FDG), also known as fluorinated deoxyglucose, is a molecule that is very similar to the chemical structure of glucose. The distribution of fluorinated deoxyglucose in the organism can vary depending on the absorption and metabolism of glucose by tissues and organs. After the positron angiography, the physiological activity image of the glucose molecule in the human body is presented, and the diagnostic function is achieved through a quantitative standard uptake value (SUV). Due to the rapid division of the cancer cells that are proliferating, the metabolic rate of the cells is abnormally increased by the regulation of the gene protein, so the fluorescein deoxyglucose can show a higher difference than the background absorption of the normal cells. Photograph taken by positron angiography Like a molecular phenomenon that can reveal organs or tissues.
然而,[氟18]-2-去氧-D-葡萄糖(F-18 Fluoro-2-Deoxyglucose,F-18-FDG)因為氟18同位素的半衰期長達109分鐘,對於腦部心理、行為、認知之量測時間可能會導致過長。因此,除了氟化去氧葡萄糖以外,開發新型藥物分子應用於腦造影技術的方法,以突破目前腦部造影領域的技術瓶頸,係為本技術領域亟欲發展的方向。 However, [Fluoro 18]-2-deoxyglucose (F-18-FDG) has a half-life of up to 109 minutes due to the fluorine 18 isotope, for brain psychology, behavior, and cognition. The measurement time may cause too long. Therefore, in addition to fluorinated deoxyglucose, the development of new drug molecules for the application of brain imaging technology to break through the current technical bottleneck in the field of brain imaging is the direction of the development of the technology field.
為達到上述的發明目的,本發明之方法所運用的技術手段,其包括以視覺(Visual)、聽覺(Auditory)、認知(Cognitive)三種方式刺激腦部,並觀察具有碳11同位素之葡萄糖分子在受試者腦部內變化的方法,其中視覺方法至少包括下列步驟:在閉眼條件控制下,讓受試者在無任何聲響及燈光昏暗之環境條件中,緊閉雙眼,讓眼球瞳孔無法接受任何外在影像,全程未思考任何問題,也未想像任何事物;對受試者注射具有碳11同位素之葡萄糖分子;對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄糖分子在受試者腦部內的第一活動圖像(a),該第一活動圖像(a)係作為標準吸收值;在視覺刺激條件控制下,讓受試者在無任何聲響及燈光柔和之環境條件中,全程張開雙眼,讓眼球瞳孔接受柔和色系之測試房間或是測試房間佈置有音樂相關符號與樂器影像,讓外在柔和色系之環境影像或是測試房間佈置有音樂相關符號與樂器影像呈現於瞳孔前,全程張開雙眼 以及想像熟悉之音樂旋律;對受試者注射具有碳11同位素之葡萄糖分子;對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄糖分子在受試者腦部內的該第二活動圖像(b);比較該第一活動圖像(a)與該第二活動圖像(b),觀察受試者在視覺刺激條件控制之前後,腦部內具有碳11同位素之葡萄糖分子活動區塊的變化;其中,該第二活動圖像(b)呈現出受試者在張開雙眼以及想像音樂旋律時,腦部內具有碳11同位素之葡萄糖分子活動圖像;較佳地,該具有碳11同位素之葡萄糖分子為碳11-2-脫氧-D-葡萄糖;較佳地,該視覺刺激條件可為但不限於單一柔和色系之測試房間、複合不同色系之測試房間、測試房間佈置有音樂相關符號與樂器影像等形式;較佳地,該腦部造影的技術為正子造影(Positron Emission Tomography,PET)或是單光子造影(Single Photon Emission Tomography,SPECT)。 In order to achieve the above object, the technical means used in the method of the present invention include stimulating the brain in three ways: visual, auditory, and cognitive (Cognitive), and observing the glucose molecule having the carbon 11 isotope. A method for changing a brain in a subject, wherein the visual method comprises at least the following steps: under the control of the closed eye condition, the subject is closed in an environmental condition without any sound and dim light, so that the pupil of the eye is unacceptable Any external image, no problem is considered in the whole process, and nothing is imagined; the subject is injected with glucose molecules with carbon 11 isotope; the subject is brain-enhanced and displayed in the display unit of the contrast instrument a first moving image (a) of a glucose molecule having a carbon 11 isotope in the brain of the subject, the first moving image (a) being used as a standard absorption value; subjecting the visual stimulation condition to a subject In an environment without any sound and soft lighting, open your eyes all the time, let the eyeball pupil accept a soft color test room or test room with music related No musical instruments and video, image or make the environment outside the testing room of pastel colors arranged music related symbols and musical instruments image presented in front of the pupil, full open eyes And imagining a familiar music melody; injecting a glucose molecule having a carbon 11 isotope into the subject; performing brain imaging on the subject, and displaying the glucose molecule having the carbon 11 isotope in the display unit of the angiography instrument at the test The second moving image (b) in the brain; comparing the first moving image (a) with the second moving image (b), observing the subject before the visual stimulation condition is controlled, the brain a change in a glucose molecular active block having a carbon 11 isotope; wherein the second active image (b) exhibits a glucose molecular activity having a carbon 11 isotope in the brain when the subject opens both eyes and imagines a musical melody Preferably, the glucose molecule having a carbon 11 isotope is carbon 11-2-deoxy-D-glucose; preferably, the visual stimulation condition may be, but not limited to, a single soft color test room, a different composite The test room and the test room of the color system are arranged in the form of music-related symbols and musical instrument images; preferably, the technique of brain imaging is Positron Emission Tomography (PET) or single photon imaging (Single Phot). On Emission Tomography, SPECT).
另一方面,本發明亦包括一種使用聽覺刺激的方法,其至少包括以下步驟:受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物;對受試者注射具有碳11同位素之葡萄糖分子;對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄糖分子在受試者腦部內的第三活動圖像(c),該第三活動圖像(c)係作為標準吸收值; 在聽覺刺激條件控制下,讓受試者在無任何聲響及燈光柔和之環境條件中,全程張開雙耳(耳道無耳塞等阻擋物)與張開雙眼,測試房間以CD等形式播放音樂或是現場人為彈奏等形式,讓雙耳接受該受測者熟悉與喜愛之柔和音樂旋律;對受試者注射具有碳11同位素之葡萄糖分子;對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄糖分子在受試者腦部內的第四活動圖像(d);比較該第四活動圖像(d)與該第三活動圖像(c),觀察受試者在聽覺刺激條件控制之前後,腦部內具有碳11同位素之葡萄糖分子活動區塊的變化。 In another aspect, the invention also includes a method of using auditory stimuli, comprising at least the steps of: subjecting the subject to control under closed eye conditions, not thinking about any problem, nor imagining anything; injecting the subject with carbon 11 a glucose molecule of an isotope; brain angiography of the subject, and displaying in the display unit of the angiography apparatus a third moving image (c) of the glucose molecule having the carbon 11 isotope in the brain of the subject, The third activity image (c) is used as a standard absorption value; Under the control of auditory stimulation conditions, the subjects can open their ears (the ear canal without earplugs and other obstacles) and open their eyes in the environment without any sound and soft lighting. The test room plays music or CD in the form of CD or the like. Artificial play and other forms, let the ears accept the soft music melody familiar and loved by the subject; inject the glucose molecule with carbon 11 isotope into the subject; perform brain imaging on the subject and display it on the contrast instrument A fourth moving image (d) of the glucose molecule having a carbon 11 isotope in the brain of the subject is displayed in the unit; comparing the fourth moving image (d) with the third moving image (c), The change in the active region of the glucose molecule with carbon 11 isotope in the brain was observed after the subject was controlled by the auditory stimulation condition.
其中,該第四活動圖像(d)呈現出受試者在張開雙眼以及聆聽音樂旋律時,腦部內具有碳11同位素之葡萄糖分子活動圖像;較佳地,該具有碳11同位素之葡萄糖分子為碳11-2-脫氧-D-葡萄糖;較佳地,該聽覺刺激條件可為但不限於CD等形式播放音樂、現場人為彈奏等形式;較佳地,該腦部造影的技術為正子造影(Positron Emission Tomography,PET)或是單光子造影(Single Photon Emission Tomography,SPECT)。 Wherein, the fourth activity image (d) presents a moving image of a glucose molecule having a carbon 11 isotope in the brain when the subject opens the eyes and listens to the music melody; preferably, the glucose having the carbon 11 isotope The molecule is carbon 11-2-deoxy-D-glucose; preferably, the auditory stimulation condition may be in the form of, but not limited to, playing music in the form of CD or the like, live playing in the field, etc.; preferably, the technique of brain imaging is Positron Emission Tomography (PET) or Single Photon Emission Tomography (SPECT).
另一方面,本發明亦包括一種使用認知刺激的方法,其至少包括以下步驟:受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物;對受試者注射具有碳11同位素之葡萄糖分子;對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出 該具有碳11同位素之葡萄糖分子在受試者腦部內的第五活動圖像(e),該第五活動圖像(e)係作為標準吸收值;在認知刺激條件控制下,讓受試者在無任何聲響及燈光柔和之環境條件中,全程張開雙耳(耳道無耳塞等阻擋物)與張開雙眼,受測者於測試房間用自己雙手以想像形式彈奏,或是以雙腳打點旋律等形式,憑空彈奏該受測者熟悉與喜愛之柔和音樂旋律;對受試者注射具有碳11同位素之葡萄糖分子;對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄糖分子在受試者腦部內的第六活動圖像(f);該第六活動圖像(f)與該第五活動圖像(e)進行比較,觀察受試者在認知刺激條件控制之前和之後,腦部內具有碳11同位素之葡萄糖分子活動區塊的變化。 In another aspect, the invention also includes a method of using cognitive stimuli, comprising at least the steps of: subjecting the subject to control under closed eye conditions, not thinking about any problem, nor imagining anything; injecting the subject with carbon 11 Isotopic glucose molecule; brain imaging of the subject and display in the display unit of the contrast instrument The fifth active image (e) of the glucose molecule having the carbon 11 isotope in the brain of the subject, the fifth active image (e) being the standard absorption value; and subjecting the cognitive stimulus condition to the test In the environment without any sound and soft lighting, open the ears (the ear canal without earplugs and other obstacles) and open the eyes, the subject in the test room with their own hands to play in the imaginary form, or with both feet In the form of melody, playing the soft music melody familiar and loved by the subject; injecting the glucose molecule with carbon 11 isotope into the subject; performing brain imaging on the subject and in the display unit of the contrast instrument Showing a sixth moving image (f) of the glucose molecule having a carbon 11 isotope in the brain of the subject; comparing the sixth moving image (f) with the fifth moving image (e), observing Subjects had changes in the active regions of glucose molecules with carbon 11 isotopes in the brain before and after control of cognitive stimulation conditions.
其中,該第六活動圖像(f)呈現出受試者在張開雙眼以及想像手部彈鋼琴、手指隨節拍動作彈奏音樂旋律時,腦部內具有碳11同位素之葡萄糖分子活動圖像;較佳地,該具有碳11同位素之葡萄糖分子為碳11-2-脫氧-D-葡萄糖;較佳地,該認知刺激條件可為但不限於受測者於測試房間用自己雙手以想像形式彈奏,或是以雙腳打點旋律等形式,憑空彈奏該受測者熟悉與喜愛之柔和音樂旋律等形式;較佳地,該腦部造影的技術為正子造影(Positron Emission Tomography,PET)或是單光子造影(Single Photon Emission Tomography,SPECT)。 Wherein, the sixth activity image (f) presents a moving image of a glucose molecule having a carbon 11 isotope in the brain when the subject opens the eyes and imagines the hand playing the piano and the finger playing the music melody with the beat action; Preferably, the glucose molecule having a carbon 11 isotope is carbon 11-2-deoxy-D-glucose; preferably, the cognitive stimulation condition may be, but is not limited to, the subject using his own hands in an imaginary form in the test room. Playing, or in the form of two-legged melody, playing the soft music melody familiar and loved by the subject; preferably, the technique of brain imaging is Positron Emission Tomography (PET) Or single photon imaging (Single Photon Emission Tomography, SPECT).
本發明係傳統核子醫學示蹤劑造影技術觀念的延續,是一種經由視覺聽覺刺激腦部認知反應圖像形成之新穎方法,藉上述技術手段的 運用,本發明提供一種新穎的腦部認知反應方法,即利用碳11-2-脫氧-D-葡萄糖([1-C-11]2-Deoxy-D-Glucose,簡稱C-11-2DG)為造影藥劑,將碳-11正子衰變同位素標誌藥物C-11-2DG注入體內,當釋放的正子遇到細胞之電子時產生「互毀反應」(annihilation reaction),形成一對方向相反的511 KeV加瑪射線,經正子造影儀測得後,再經電腦運算重組出影像。再者,本發明係屬核醫藥物產業之藥物研發與心理認知腦部功能部位影像之創新研究,除了應用於核醫產業藥物的新用途之外,在心理認知與管理策略等領域的應用上,本發明的技術亦會是不可或缺。 The invention is a continuation of the traditional nuclear medicine tracer imaging technology concept, and is a novel method for stimulating brain cognitive response image formation through visual hearing, by the above technical means The invention provides a novel brain cognitive reaction method, which utilizes carbon 11-2-deoxy-D-glucose ([1-C-11]2-Deoxy-D-Glucose, abbreviated as C-11-2DG). The contrast agent injects the carbon-11 positron decay isotope marker drug C-11-2DG into the body, and when the released positron encounters the electrons of the cell, an "annihilation reaction" occurs, forming a pair of 511 KeV plus After the ray is measured by the positron imager, the image is reconstructed by computer operation. Furthermore, the present invention relates to an innovative research on the drug development and psychological cognition of the functional parts of the brain in the nuclear medicine industry, in addition to the new use of drugs in the nuclear medicine industry, in the fields of psychological cognition and management strategies. The technology of the present invention may also be indispensable.
(a)‧‧‧第一活動圖像 (a) ‧ ‧ first activity image
(b)‧‧‧第二活動圖像 (b) ‧ ‧ second activity image
(c)‧‧‧第三活動圖像 (c) ‧ ‧ third activity image
(d)‧‧‧第四活動圖像 (d) ‧ ‧ fourth event image
(e)‧‧‧第五活動圖像 (e) ‧ ‧ fifth event image
(f)‧‧‧第六活動圖像 (f) ‧ ‧ sixth activity image
第1圖係本發明之方法中腦部接受刺激前後的葡萄糖分子活動區塊變化對照圖。 Fig. 1 is a comparison diagram of changes in glucose molecular activity blocks before and after stimulation of the brain in the method of the present invention.
本發明係一種刺激腦部認知反應圖像形成之方法,其包括下列步驟: The present invention is a method for stimulating brain cognitive response image formation, which comprises the following steps:
步驟11:受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物。 Step 11: Under the control of closed eye conditions, the subject did not think about any problems and did not imagine anything.
步驟12:對受試者注射具有碳11同位素之葡萄糖分子,依據本發明,所述之具有碳11同位素之葡萄醣分子可為碳11-2-脫氧-D-葡萄糖或其他可替代之物質。 Step 12: The subject is injected with a glucose molecule having a carbon 11 isotope. According to the present invention, the glucose molecule having the carbon 11 isotope may be carbon 11-2-deoxy-D-glucose or other alternative substance.
步驟13:對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出具有碳11同位素之葡萄糖分子在受試者腦部內的第一活動圖像(a),此第一活動圖像(a)係用以作為標準吸收值,依據本發明,腦部造影的 技術可為但不限於正子造影(Positron Emission Tomography,PET)、單光子造影(Single Photon Emission Tomography,SPECT)及其他可替代之技術。 Step 13: performing brain imaging on the subject, and displaying a first active image (a) of the glucose molecule having the carbon 11 isotope in the brain of the subject in the display unit of the contrast instrument, the first activity Image (a) is used as a standard absorption value, according to the present invention, brain angiography Techniques can be, but are not limited to, Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and other alternative techniques.
步驟14:受試者在視覺刺激條件控制下,全程張開雙眼以及想像音樂旋律,依據本發明,所述之該視覺刺激條件可為但不限於單一柔和色系之測試房間、複合不同色系之測試房間、測試房間佈置有音樂相關符號與樂器影像等形式;此外,所想像的音樂旋律以受試者本身已熟知的音樂旋律較佳。 Step 14: The subject opens the eyes and imagines the music melody in the whole process under the control of the visual stimulation condition. According to the present invention, the visual stimulation condition may be, but not limited to, a test room of a single soft color system, and a composite color system. The test room and the test room are arranged in the form of music-related symbols and musical instrument images; in addition, the imaginary music melody is preferably a musical melody that is well known to the subject.
步驟15:對受試者注射具有碳11同位素之葡萄糖分子,依據本發明,所述之具有碳11同位素之葡萄糖分子可為碳11-2-脫氧-D-葡萄糖或其他可替代之物質。 Step 15: The subject is injected with a glucose molecule having a carbon 11 isotope. According to the present invention, the glucose molecule having the carbon 11 isotope may be carbon 11-2-deoxy-D-glucose or other alternative substance.
步驟16:對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出具有碳11同位素之葡萄糖分子在受試者腦部內的第二活動圖像(b),依據本發明,腦部造影的技術可為但不限於正子造影(Positron Emission Tomography,PET)、單光子造影(Single Photon Emission Tomography,SPECT)及其他可替代之技術。。 Step 16: performing brain imaging on the subject, and displaying a second moving image (b) of the glucose molecule having the carbon 11 isotope in the brain of the subject in the display unit of the contrast instrument, according to the present invention, Techniques for brain imaging may be, but are not limited to, Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and other alternative techniques. .
步驟17:第二活動圖像(b)與第一活動圖像(a)進行比較,觀察受試者在視覺刺激條件控制之前和之後,腦部內具有碳11同位素之葡萄糖分子活動的變化。 Step 17: The second moving image (b) is compared with the first moving image (a) to observe changes in the glucose molecule activity of the carbon 11 isotope in the brain before and after the control of the visual stimulation condition.
在另一方面中,本發明之方法所運用的技術手段亦可包括下列步驟: In another aspect, the technical means utilized by the method of the present invention may also include the following steps:
步驟21:受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物。 Step 21: Under the control of closed eye conditions, the subject did not think about any problems and did not imagine anything.
步驟22:對受試者注射具有碳11同位素之葡萄糖分子,依據本發明,所述之具有碳11同位素之葡萄糖分子可為碳11-2-脫氧-D-葡萄糖或其他可替代之物質。 Step 22: The subject is injected with a glucose molecule having a carbon 11 isotope. According to the present invention, the glucose molecule having the carbon 11 isotope may be carbon 11-2-deoxy-D-glucose or other alternative substance.
步驟23:對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄醣分子在受試者腦部內的第三活動圖像(c),此第三活動圖像(c)用以作為標準吸收值,依據本發明,腦部造影的技術可為但不限於正子造影(Positron Emission Tomography,PET)、單光子造影(Single Photon Emission Tomography,SPECT)及其他可替代之技術。 Step 23: performing brain imaging on the subject, and displaying a third active image (c) of the glucose molecule having carbon 11 isotope in the brain of the subject in the display unit of the contrast instrument, this third The moving image (c) is used as a standard absorption value. According to the present invention, the technique of brain imaging can be, but not limited to, Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and the like. Alternative technology.
步驟24:受試者在聽覺刺激條件控制下,全程張開雙眼以及聆聽音樂旋律,依據本發明,所述之該聽覺刺激條件可為但不限於CD等形式播放音樂、現場人為彈奏等形式;此外,受試者所聆聽的音樂以受試者本身已熟知的音樂較佳。 Step 24: The subject opens the eyes and listens to the music melody in the whole process under the control of the auditory stimulation condition. According to the present invention, the auditory stimulation condition may be, but is not limited to, playing music in the form of CD or the like, and playing in the field; In addition, the music the subject is listening to is better known to the music that the subject himself is familiar with.
步驟25:對受試者注射具有碳11同位素之葡萄糖分子,依據本發明,所述之具有碳11同位素之葡萄糖分子可為碳11-2-脫氧-D-葡萄糖或其他可替代之物質。 Step 25: The subject is injected with a glucose molecule having a carbon 11 isotope. According to the present invention, the glucose molecule having the carbon 11 isotope may be carbon 11-2-deoxy-D-glucose or other alternative substance.
步驟26:對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄醣分子在受試者腦部內的第四活動圖像(d),依據本發明,腦部造影的技術可為但不限於正子造影(Positron Emission Tomography,PET)、單光子造影(Single Photon Emission Tomography,SPECT)及其他可替代之技術。 Step 26: performing brain imaging on the subject, and displaying a fourth moving image (d) of the glucose molecule having the carbon 11 isotope in the brain of the subject in the display unit of the contrast instrument, according to the present invention The technique of brain imaging may be, but not limited to, Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and other alternative technologies.
步驟27:第四活動圖像(d)與該第三活動圖像(c)進行比較,觀察受試者在聽覺刺激條件控制之前和之後,腦部內具有碳11同位素之葡 萄糖分子活動的變化。 Step 27: The fourth moving image (d) is compared with the third moving image (c), and the subject is observed to have a carbon 11 isotope in the brain before and after the auditory stimulation condition is controlled. Changes in the activity of glucose molecules.
在又一方面中,本發明之方法所運用的技術手段亦可包括下列步驟: In yet another aspect, the technical means utilized by the method of the present invention may also include the following steps:
步驟31:受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物。 Step 31: Under the control of closed eye conditions, the subject did not think about any problems and did not imagine anything.
步驟32:對受試者注射具有碳11同位素之葡萄糖分子,依據本發明,所述之具有碳11同位素之葡萄糖分子可為碳11-2-脫氧-D-葡萄糖或其他可替代之物質。 Step 32: The subject is injected with a glucose molecule having a carbon 11 isotope. According to the present invention, the glucose molecule having the carbon 11 isotope may be carbon 11-2-deoxy-D-glucose or other alternative substance.
步驟33:對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄糖分子在受試者腦部內的第五活動圖像(e),該第五活動圖像(e)用以作為標準吸收值,依據本發明,腦部造影的技術可為但不限於正子造影(Positron Emission Tomography,PET)、單光子造影(Single Photon Emission Tomography,SPECT)及其他可替代之技術。 Step 33: performing brain imaging on the subject, and displaying a fifth moving image (e) of the glucose molecule having a carbon 11 isotope in the brain of the subject in the display unit of the contrast instrument, the fifth The moving image (e) is used as a standard absorption value. According to the present invention, the technique of brain imaging can be, but not limited to, Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and the like. Alternative technology.
步驟34:受試者在認知刺激條件控制下,全程張開雙眼以及想像手部彈鋼琴、手指隨節拍動作彈奏音樂旋律,依據本發明,所述之該認知刺激條件可為但不限於受測者於測試房間用自己雙手以想像形式彈奏,或是以雙腳打點旋律等形式,憑空彈奏該受測者熟悉與喜愛之柔和音樂旋律等形式;此外,受試者所聆聽的音樂以受試者本身已熟知的音樂較佳。 Step 34: Under the control of the cognitive stimulation condition, the subject opens the eyes and imagines the hand playing the piano, and the finger plays the music melody with the beat action. According to the present invention, the cognitive stimulation condition may be but not limited to the measured In the test room, play with his own hands in the form of imaginary, or in the form of two-legged melody, playing the soft music melody familiar and loved by the subject; and the music the subject listens to. Music is well known to the subject itself.
步驟35:對受試者注射具有碳11同位素之葡萄糖分子,依據本發明,所述之具有碳11同位素之葡萄糖分子可為碳11-2-脫氧-D-葡萄糖或其他可替代之物質。 Step 35: The subject is injected with a glucose molecule having a carbon 11 isotope. According to the present invention, the glucose molecule having the carbon 11 isotope may be carbon 11-2-deoxy-D-glucose or other alternative substance.
步驟36:對受試者進行腦部造影,並於造影儀器的顯示單元中顯示出該具有碳11同位素之葡萄糖分子在受試者腦部內的第六活動圖像(f),依據本發明,腦部造影的技術可為但不限於正子造影(Positron Emission Tomography,PET)、單光子造影(Single Photon Emission Tomography,SPECT)及其他可替代之技術。 Step 36: performing brain imaging on the subject, and displaying a sixth moving image (f) of the glucose molecule having carbon 11 isotope in the brain of the subject in the display unit of the contrast instrument, according to the present invention The technique of brain imaging may be, but not limited to, Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and other alternative technologies.
步驟37:該第六活動圖像(f)與該第五活動圖像(e)進行比較,觀察受試者在認知刺激條件控制之前和之後,腦部內具有碳11同位素之葡萄糖分子活動的變化。 Step 37: comparing the sixth activity image (f) with the fifth activity image (e), observing the activity of the glucose molecule having a carbon 11 isotope in the brain before and after the cognitive stimulation condition is controlled. Variety.
葡萄糖是供給大腦活動的主要能量來源,大腦內部的葡萄糖代謝狀況在一定程度上可以反映腦功能的狀況。葡萄糖代謝水平的下降可表示大腦局部神經元活動受到抑制,其為腦功能失調的其中一種表現。作為一種葡萄糖類似物,例如碳11-2-脫氧-D-葡萄糖,將為腦細胞中的葡萄糖高利用率細胞所攝取,在此類細胞內,磷酸化反應將會阻止葡萄糖分子以原有的形式從細胞中釋放出來。 Glucose is the main source of energy for brain activity. The metabolism of glucose inside the brain can reflect the state of brain function to a certain extent. A decrease in the level of glucose metabolism may indicate inhibition of local neuronal activity in the brain, which is one of the manifestations of brain dysfunction. As a glucose analog, such as carbon 11-2-deoxy-D-glucose, it will be taken up by high-yield glucose cells in brain cells. In such cells, phosphorylation will prevent glucose molecules from becoming intact. The form is released from the cell.
由於葡萄糖分子結構中的2’位置的氧乃是後續糖酵解所必需的,因而在細胞內的碳11-2-脫氧-D-葡萄糖無法繼續代謝,而在放射性衰變之前,碳11-2-脫氧-D-葡萄糖經磷酸化反應後所形成的碳11-2-脫氧-D-葡萄糖-6-磷酸將不會發生糖酵解。藉此,碳11-2-脫氧-D-葡萄糖的分布情況就會適當地反映出腦細胞中葡萄糖高利用率細胞對葡萄糖分子的攝取情況,以及經磷酸化之葡萄糖分子的分布情況。在碳11-2-脫氧-D-葡萄糖發生衰變之前,碳11-2-脫氧-D-葡萄糖的代謝分解或利用會因為其分子結構中的2’位置為缺氧而受到抑制。具放射性的碳11同位素透過正子輻射作用,會完 全衰退成硼11原子,而碳11原子衰退成為硼11原子的半衰期約為20分鐘。碳11同位素發生放射性衰變之後,將轉變為硼11而不再產生511 KeV加瑪射線。 Since the oxygen at the 2' position in the molecular structure of the glucose is necessary for subsequent glycolysis, the carbon 11-2-deoxy-D-glucose in the cell cannot continue to be metabolized, and before the radioactive decay, the carbon 11-2 - Carbon 11-2-deoxy-D-glucose-6-phosphate formed by dephosphorylation of D-glucose will not undergo glycolysis. Thereby, the distribution of carbon 11-2-deoxy-D-glucose appropriately reflects the uptake of glucose molecules by glucose-utilized cells in brain cells, and the distribution of phosphorylated glucose molecules. Prior to the decay of carbon 11-2-deoxy-D-glucose, the metabolic decomposition or utilization of carbon 11-2-deoxy-D-glucose is inhibited by the hypoxia of the 2' position in its molecular structure. Radioactive carbon 11 isotope through positron radiation The total decay is 11 atoms of boron, and the half-life of the carbon 11 atom decaying to boron 11 atom is about 20 minutes. After the carbon 11 isotope undergoes radioactive decay, it will be converted to boron 11 and no longer produce 511 KeV gamma rays.
藉由上述技術手段之運用,本發明係為經由視覺、聽覺、認知刺激腦部認知反應圖像形成的新穎方法,藉由檢測碳11-2-脫氧-D-葡萄糖於腦中葡萄糖代謝影像的直接資訊,反應出人腦面對視覺、聽覺、認知刺激時之腦部功能影像,此為本發明之主要目的。 Through the use of the above technical means, the present invention is a novel method for stimulating brain cognitive response image formation through visual, auditory and cognitive sensation, by detecting carbon 11-2-deoxy-D-glucose in the brain for glucose metabolism imaging. The direct information reflects the functional image of the brain in the face of visual, auditory and cognitive stimuli. This is the main purpose of the invention.
使用藥物:碳-11-2-脫氧-D-葡萄糖([1-C-11]2-Deoxy-D-Glucose(以下簡稱C-11-2DG))。 The drug was used: carbon-11-2-deoxy-D-glucose ([1-C-11]2-Deoxy-D-Glucose (hereinafter referred to as C-11-2DG)).
藥劑規格:配製為等張(isotonic)之核醫級無菌注射劑,由PET中心之自動合成盒所調製,放射化學純度大於95%。 Pharmacy specification: Prepared as an isotonic nuclear-grade sterile injection, prepared by the automatic synthesis box of PET Center, with a radiochemical purity greater than 95%.
試驗流程(一): Test process (1):
1.受試者先空腹6小時。 1. The subject was fasted for 6 hours.
2.受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物。 2. Under the control of closed eye conditions, the subject did not think about any problems and did not imagine anything.
3.對受試者進行靜脈注射C-11-2DG,劑量為16~20 mCi。 3. Subjects were given intravenous C-11-2DG at a dose of 16-20 mCi.
4.注射後,受試者在安靜狀態下休息約45分鐘,排尿後仰臥在檢查床上,再以PET造影(例如GE Discovery LS型)進行腦部掃描。圖像經衰減校正影像處理,進行圖像重建,顯示出具有C-11-2DG在受試者腦部內的活動圖像1,活動圖像1係用以作為標準吸收值。 4. After the injection, the subject rested in a quiet state for about 45 minutes, urinating and lying on the examination bed, and then performing a brain scan with PET imaging (for example, GE Discovery LS type). The image was subjected to attenuation-corrected image processing for image reconstruction, showing a moving image 1 having C-11-2DG in the brain of the subject, and moving image 1 was used as a standard absorption value.
5.受試者在視覺刺激條件控制下,全程張開雙眼以及想像 本身已熟知的音樂旋律。 5. Subjects open their eyes and imagine the whole process under the control of visual stimulation conditions. A musical melody that is already well known.
6.對受試者進行靜脈注射C-11-2DG,劑量為16~20 mCi。 6. Subjects were given intravenous C-11-2DG at a dose of 16-20 mCi.
7.步驟6:注射後,受試者在安靜狀態下休息約45分鐘,排尿後仰臥在檢查床上,再以PET造影(例如GE Discovery LS型)進行腦部掃描。圖像經衰減校正影像處理,進行圖像重建,顯示出具有C-11-2DG在受試者腦部內的活動圖像2。 7. Step 6: After the injection, the subject rests in a quiet state for about 45 minutes, urinates and lies on the examination bed, and then performs a brain scan with PET imaging (for example, GE Discovery LS type). The image is subjected to attenuation-corrected image processing for image reconstruction, showing a moving image 2 with C-11-2DG in the subject's brain.
8.活動圖像2與活動圖像1進行比較,觀察受試者在視覺刺激條件控制之前和之後,腦部內C-11-2DG活動的變化。 8. The moving image 2 was compared with the moving image 1 to observe changes in the C-11-2DG activity in the brain before and after the visual stimulation condition control.
試驗流程(二): Test process (2):
1.受試者先空腹6小時。 1. The subject was fasted for 6 hours.
2.受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物。 2. Under the control of closed eye conditions, the subject did not think about any problems and did not imagine anything.
3.對受試者進行靜脈注射C-11-2DG,劑量為16~20 mCi。 3. Subjects were given intravenous C-11-2DG at a dose of 16-20 mCi.
4.注射後,受試者在安靜狀態下休息約45分鐘,排尿後仰臥在檢查床上,再以PET造影(例如GE Discovery LS型)進行腦部掃描。圖像經衰減校正影像處理,進行圖像重建,顯示出具有C-11-2DG在受試者腦部內的活動圖像3,活動圖像3係用以作為標準吸收值。 4. After the injection, the subject rested in a quiet state for about 45 minutes, urinating and lying on the examination bed, and then performing a brain scan with PET imaging (for example, GE Discovery LS type). The image was subjected to attenuation-corrected image processing for image reconstruction, showing a moving image 3 having C-11-2DG in the brain of the subject, and moving image 3 was used as a standard absorption value.
5.受試者在聽覺刺激條件控制下,全程張開雙眼以及聆聽本身已熟知的音樂旋律。 5. Under the control of auditory stimulation conditions, the subject opens his eyes and listens to the music melody he is already familiar with.
6.對受試者進行靜脈注射C-11-2DG,劑量為16~20 mCi。 6. Subjects were given intravenous C-11-2DG at a dose of 16-20 mCi.
7.注射後,受試者在安靜狀態下休息約45分鐘,排尿後仰臥在檢查床上,再以PET造影(例如GE Discovery LS型)進行腦部掃描。 圖像經衰減校正影像處理,進行圖像重建,顯示出具有C-11-2DG在受試者腦部內的活動圖像4。 7. After the injection, the subject rested in a quiet state for about 45 minutes, urinating and lying on the examination bed, and then performing a brain scan with PET imaging (for example, GE Discovery LS type). The image is subjected to attenuation-corrected image processing for image reconstruction, showing a moving image 4 having C-11-2DG in the subject's brain.
8.活動圖像4與活動圖像3進行比較,觀察受試者在聽覺刺激條件控制之前和之後,腦部內C-11-2DG活動的變化。 8. The moving image 4 is compared with the moving image 3 to observe changes in the C-11-2DG activity in the brain before and after the subject is controlled by the auditory stimulation condition.
試驗流程(三): Test procedure (3):
1.受試者先空腹6小時。 1. The subject was fasted for 6 hours.
2.受試者在閉眼條件控制下,全程未思考任何問題,也未想像任何事物。 2. Under the control of closed eye conditions, the subject did not think about any problems and did not imagine anything.
3.對受試者進行靜脈注射C-11-2DG,劑量為16~20 mCi。 3. Subjects were given intravenous C-11-2DG at a dose of 16-20 mCi.
4.注射後,受試者在安靜狀態下休息約45分鐘,排尿後仰臥在檢查床上,再以PET造影(例如GE Discovery LS型)進行腦部掃描。圖像經衰減校正影像處理,進行圖像重建,顯示出具有C-11-2DG在受試者腦部內的活動圖像5,活動圖像5係用以作為標準吸收值。 4. After the injection, the subject rested in a quiet state for about 45 minutes, urinating and lying on the examination bed, and then performing a brain scan with PET imaging (for example, GE Discovery LS type). The image was subjected to attenuation-corrected image processing for image reconstruction, showing a moving image 5 having C-11-2DG in the brain of the subject, and the moving image 5 was used as a standard absorption value.
5.受試者在認知刺激條件控制下,全程張開雙眼以及想像手部彈鋼琴、手指隨節拍動作彈奏本身已熟知音樂旋律。 5. Subjects under the control of cognitive stimulation conditions, open the eyes all the way and imagine the hand playing the piano, the finger playing with the beat action itself is already familiar with the music melody.
6.對受試者進行靜脈注射C-11-2DG,劑量為16~20 mCi。 6. Subjects were given intravenous C-11-2DG at a dose of 16-20 mCi.
7.注射後,受試者在安靜狀態下休息約45分鐘,排尿後仰臥在檢查床上,再以PET造影(例如GE Discovery LS型)進行腦部掃描。圖像經衰減校正影像處理,進行圖像重建,顯示出具有C-11-2DG在受試者腦部內的活動圖像6。 7. After the injection, the subject rested in a quiet state for about 45 minutes, urinating and lying on the examination bed, and then performing a brain scan with PET imaging (for example, GE Discovery LS type). The image is subjected to attenuation-corrected image processing for image reconstruction, showing a moving image 6 having C-11-2DG in the subject's brain.
8.活動圖像6與活動圖像5進行比較,觀察受試者在認知刺激條件控制之前和之後,腦部內C-11-2DG活動的變化。 8. The moving image 6 was compared with the moving image 5 to observe changes in C-11-2DG activity in the brain before and after control of cognitive stimulation conditions.
請參閱第1圖所示,其係為三種試驗過程的第一至第六活動圖像(a)、(b)、(c)、(d)、(e)、(f),其顯示三種刺激條件前後,腦部內C-11-2DG的代謝幅度變化。三種試驗結果中,未經刺激時與經過刺激後的C-11-2DG在腦部的作用位置均大致相似,但C-11-2DG代謝量均有大幅增加的趨勢。 Referring to Figure 1, it is the first to sixth moving images (a), (b), (c), (d), (e), (f) of the three test procedures, which show three The metabolic amplitude of C-11-2DG in the brain changed before and after the stimulation condition. Among the three test results, the position of C-11-2DG in the brain after stimulation was similar to that in the brain, but the metabolism of C-11-2DG increased significantly.
在視覺刺激條件控制下,大腦之後腦區塊及前額葉區塊之葡萄糖代謝均明顯增加,如第1圖中視覺(Visual)部分所呈現受測者測試前受PET影像之差別。但是以fMRI等先前技術之傳統方式,只能證明血流速度增加之區塊,沒有以直接證據之方式證明與呈現。 Under the control of visual stimulation conditions, the glucose metabolism in the brain and prefrontal regions of the brain increased significantly, as shown in the visual (Visual) section of Figure 1, the difference in PET images before the test. However, in the traditional way of prior art such as fMRI, only the block with increased blood flow velocity can be proved, and it is not proved and presented by direct evidence.
在聽覺刺激條件控制下,大腦兩側之腦區塊之葡萄糖代謝均明顯增加,如第1圖中聽覺(Auditory)部分所呈現受測者測試前受PET影像之差別。但是以fMRI等先前技術之傳統方式,只能證明血流速度增加之區塊,沒有以直接證據之方式證明與呈現。 Under the control of auditory stimulation conditions, the glucose metabolism in the brain blocks on both sides of the brain is significantly increased, as shown in the Auditory (Auditory) section of Fig. 1 by the difference in PET images before the test. However, in the traditional way of prior art such as fMRI, only the block with increased blood flow velocity can be proved, and it is not proved and presented by direct evidence.
在認知激條件控制下,大腦之後腦區塊之葡萄糖代謝明顯增加,但前額葉區塊無明顯增加,如第1圖中認知(Cognitive)部分所呈現受測者測試前受PET影像之差別。但是以fMRI等先前技術之傳統方式,只能證明血流速度增加之區塊,沒有以直接證據之方式證明與呈現。 Under the control of cognitive conditions, the glucose metabolism in the brain block of the brain increased significantly, but the prefrontal block did not increase significantly, as shown in the Cognitive part of Figure 1, the difference between the PET images before the test. . However, in the traditional way of prior art such as fMRI, only the block with increased blood flow velocity can be proved, and it is not proved and presented by direct evidence.
以上所述僅是本發明的較佳實施例而已,並非對本發明做任何形式上的限制,雖然本發明已以較佳實施例揭露如上,然而並非用以限定本發明,任何熟悉本專業的技術人員,在不脫離本發明技術方案的範圍內,當可利用上述揭示的技術內容作出些許更動或修飾為等同變化的等效實施例,但凡是未脫離本發明技術方案的內容,依據本發明的技術實質對以上實施例所作的任何簡單修改、等同變化與修飾,均仍屬於本發明技術 方案的範圍內。 The above is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. Although the present invention has been disclosed in the above preferred embodiments, it is not intended to limit the present invention. A person skilled in the art can make some modifications or modifications to equivalent embodiments by using the above-disclosed technical contents without departing from the technical scope of the present invention. Technical Substantials Any simple modifications, equivalent variations, and modifications made to the above embodiments are still within the skill of the present invention. Within the scope of the program.
(a)‧‧‧第一活動圖像 (a) ‧ ‧ first activity image
(b)‧‧‧第二活動圖像 (b) ‧ ‧ second activity image
(c)‧‧‧第三活動圖像 (c) ‧ ‧ third activity image
(d)‧‧‧第四活動圖像 (d) ‧ ‧ fourth event image
(e)‧‧‧第五活動圖像 (e) ‧ ‧ fifth event image
(f)‧‧‧第六活動圖像 (f) ‧ ‧ sixth activity image
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